Calcium channel subtypes differentially regulate fusion pore stability and expansion.

Various studies have focused in the relative contribution of different voltage-activated Ca(2+) channels (VACC) to total transmitter release. However, how Ca(2+) entry through a given VACC subtype defines the pattern of individual exocytotic events remains unknown. To address this question, we have used amperometry in bovine chromaffin cells. L, N, and P/Q channels were individually or jointly blocked with furnidipine, omega-conotoxin GVIA, omega-agatoxin IVA, or omega-conotoxin MVIIC. The three channel types contributed similarly to cytosolic Ca(2+) signals induced by 70 mmol/L K(+). However, they exhibited different contributions to the frequency of exocytotic events and they were shown to differently regulate the final steps of the exocytosis. When compared with the other VACC subtypes, Ca(2+) entry through P/Q channels effectively induced exocytosis, it decreased fusion pore stability and accelerated its expansion. Conversely, Ca(2+) entry through N channels was less efficient in inducing exocytotic events, also slowing fusion pore expansion. Finally, Ca(2+) entry through L channels inefficiently induced exocytosis, and the individual blockade of this channel significantly modified fusion pore dynamics. The distance between a given VACC subtype and the release sites could account for the differential effects of the distinct VACC on the fusion pore dynamics.